What is the use of Gliclazide (Gliclazide) MR in patients with Chronic Kidney Disease (CKD)?

Gliclazide MR in Chronic Kidney Disease

Gliclazide modified release (MR) is a preferred sulfonylurea for patients with chronic kidney disease due to its favorable safety profile, particularly its lower risk of hypoglycemia and minimal dose adjustment requirements in renal impairment. 1, 2

Safety Profile in CKD

• Gliclazide MR has demonstrated a very good safety profile in patients with impaired renal function, with a low incidence of hypoglycemic episodes similar to that observed in the general population 2
• Unlike first-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) which should be avoided in CKD, gliclazide is preferred because it does not have active metabolites that would increase hypoglycemia risk in reduced kidney function 1
• The drug is extensively metabolized with only 4% of total drug clearance occurring through renal elimination, making it safer in the setting of reduced kidney function 3

Efficacy in CKD

• Gliclazide MR provides effective 24-hour glycemic control with once-daily dosing, which can improve medication adherence in patients with multiple comorbidities 4
• Studies have shown that gliclazide MR significantly reduces HbA1c by approximately 0.46% over a 2-year period, with similar efficacy when used as monotherapy or in combination therapy 2
• The modified release formulation provides progressive drug release that parallels the 24-hour glycemic profile in patients with type 2 diabetes 4

Dosing Considerations in CKD

• Unlike metformin, which is contraindicated when serum creatinine exceeds 1.5 mg/dL in men and 1.4 mg/dL in women, gliclazide MR can be used in patients with reduced kidney function 1
• The standard dosing range for gliclazide MR is 30-120 mg once daily, with minimal need for dose adjustment in CKD patients 2, 4

Place in Therapy for Diabetic CKD Patients

• Current guidelines recommend a stepwise approach for glycemic management in CKD:
  1. Metformin is recommended as first-line therapy for patients with T2D, CKD, and eGFR ≥30 ml/min/1.73 m² (with dose reduction to 1000 mg daily for eGFR 30-44 ml/min/1.73 m²) 1
  2. SGLT2 inhibitors are recommended for patients with T2D, CKD, and eGFR ≥20 ml/min/1.73 m² 1
  3. GLP-1 receptor agonists are recommended for patients who have not achieved glycemic targets despite metformin and SGLT2i, or who cannot use these medications 1
  4. Gliclazide MR can be considered as an alternative agent when other preferred medications cannot be used or when additional glycemic control is needed 1, 5

Advantages Over Other Sulfonylureas

• Gliclazide MR has shown lower rates of hypoglycemia compared to other sulfonylureas 5, 4
• It demonstrates minimal weight gain compared to some other sulfonylureas 5, 4
• The drug has potential additional benefits including antioxidant properties and effects on platelet function that may be beneficial in patients with diabetic complications 4, 3

Monitoring Recommendations

• Regular monitoring of glycemic control is recommended, with HbA1c measurements twice per year or more frequently if targets are not met 1
• Be aware that HbA1c measurement accuracy declines with advanced CKD (G4-G5), particularly in dialysis patients 1
• Consider more frequent blood glucose monitoring when using sulfonylureas including gliclazide MR in patients with CKD to detect and prevent hypoglycemia 1

Common Pitfalls and Caveats

• Despite its favorable profile, gliclazide MR still carries some risk of hypoglycemia, particularly when combined with other glucose-lowering medications 4
• Current guidelines prioritize SGLT2 inhibitors and GLP-1 receptor agonists over sulfonylureas due to their proven cardiovascular and renal benefits 1
• When using gliclazide MR in elderly CKD patients, start with lower doses and monitor more closely for hypoglycemia, even though studies suggest similar safety in this population 2, 4